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Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss
BACKGROUND: The hyperinsulinemia of obesity is a function of both increased pancreatic insulin secretion and decreased insulin clearance, and contributes to cardiovascular risk. Whilst weight loss is known to enhance insulin clearance, there is a paucity of data concerning the underlying mechanisms....
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546319/ https://www.ncbi.nlm.nih.gov/pubmed/26297500 http://dx.doi.org/10.1186/s12933-015-0276-2 |
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author | Straznicky, Nora E. Grima, Mariee T. Sari, Carolina I. Lambert, Elisabeth A. Phillips, Sarah E. Eikelis, Nina Kobayashi, Daisuke Hering, Dagmara Mariani, Justin A. Dixon, John B. Nestel, Paul J. Karapanagiotidis, Sofie Schlaich, Markus P. Lambert, Gavin W. |
author_facet | Straznicky, Nora E. Grima, Mariee T. Sari, Carolina I. Lambert, Elisabeth A. Phillips, Sarah E. Eikelis, Nina Kobayashi, Daisuke Hering, Dagmara Mariani, Justin A. Dixon, John B. Nestel, Paul J. Karapanagiotidis, Sofie Schlaich, Markus P. Lambert, Gavin W. |
author_sort | Straznicky, Nora E. |
collection | PubMed |
description | BACKGROUND: The hyperinsulinemia of obesity is a function of both increased pancreatic insulin secretion and decreased insulin clearance, and contributes to cardiovascular risk. Whilst weight loss is known to enhance insulin clearance, there is a paucity of data concerning the underlying mechanisms. This study was conducted to examine the inter-relationships between changes in sympathetic nervous system (SNS) activity, vascular function and insulin clearance during a weight loss program. METHODS: Seventeen non-smoking, un-medicated individuals aged 55 ± 1 years (mean ± SEM), body mass index (BMI) 33.9 ± 1.7 kg/m(2), underwent a 4-month hypocaloric diet (HCD), using a modified Dietary Approaches to Stop Hypertension diet, whilst seventeen age- and BMI-matched subjects acted as controls. Insulin sensitivity and insulin clearance were assessed via euglycemic hyperinsulinemic clamp (exogenous insulin clearance); hepatic insulin extraction was calculated as fasting C-peptide to insulin ratio (endogenous insulin clearance); SNS activity was quantified by microneurographic nerve recordings of muscle sympathetic nerve activity (MSNA) and whole-body norepinephrine kinetics; and vascular function by calf venous occlusion plethysmography and finger arterial tonometry. RESULTS: Weight loss averaged −8.3 ± 0.6 % of body weight in the HCD group and was accompanied by increased clamp-derived glucose utilization (by 20 ± 9 %, P = 0.04) and exogenous insulin clearance (by 12 ± 5 %, P = 0.02). Hepatic insulin extraction increased from 6.3 ± 0.8 to 7.1 ± 0.9 (P = 0.09). Arterial norepinephrine concentration decreased by −12 ± 5 %, whole-body norepinephrine spillover rate by −14 ± 8 %, and MSNA by −9 ± 5 bursts per 100 heartbeats in the HCD group (P all >0.05 versus control group). Step-wise regression analysis revealed a bidirectional relationship between enhanced exogenous insulin clearance post weight loss and reduction in calf vascular resistance (r = −0.63, P = 0.01) which explained 40 % of the variance. Increase in hepatic insulin extraction was predicted by enhanced finger reactive hyperaemic response (P = 0.006) and improvement in oral glucose tolerance (P = 0.002) which together explained 64 % of the variance. CONCLUSIONS: Insulin clearance is independently and reciprocally associated with changes in vascular function during weight loss intervention. Trial registration ClinicalTrials.gov: NCT01771042 and NCT00408850 |
format | Online Article Text |
id | pubmed-4546319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45463192015-08-23 Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss Straznicky, Nora E. Grima, Mariee T. Sari, Carolina I. Lambert, Elisabeth A. Phillips, Sarah E. Eikelis, Nina Kobayashi, Daisuke Hering, Dagmara Mariani, Justin A. Dixon, John B. Nestel, Paul J. Karapanagiotidis, Sofie Schlaich, Markus P. Lambert, Gavin W. Cardiovasc Diabetol Original Investigation BACKGROUND: The hyperinsulinemia of obesity is a function of both increased pancreatic insulin secretion and decreased insulin clearance, and contributes to cardiovascular risk. Whilst weight loss is known to enhance insulin clearance, there is a paucity of data concerning the underlying mechanisms. This study was conducted to examine the inter-relationships between changes in sympathetic nervous system (SNS) activity, vascular function and insulin clearance during a weight loss program. METHODS: Seventeen non-smoking, un-medicated individuals aged 55 ± 1 years (mean ± SEM), body mass index (BMI) 33.9 ± 1.7 kg/m(2), underwent a 4-month hypocaloric diet (HCD), using a modified Dietary Approaches to Stop Hypertension diet, whilst seventeen age- and BMI-matched subjects acted as controls. Insulin sensitivity and insulin clearance were assessed via euglycemic hyperinsulinemic clamp (exogenous insulin clearance); hepatic insulin extraction was calculated as fasting C-peptide to insulin ratio (endogenous insulin clearance); SNS activity was quantified by microneurographic nerve recordings of muscle sympathetic nerve activity (MSNA) and whole-body norepinephrine kinetics; and vascular function by calf venous occlusion plethysmography and finger arterial tonometry. RESULTS: Weight loss averaged −8.3 ± 0.6 % of body weight in the HCD group and was accompanied by increased clamp-derived glucose utilization (by 20 ± 9 %, P = 0.04) and exogenous insulin clearance (by 12 ± 5 %, P = 0.02). Hepatic insulin extraction increased from 6.3 ± 0.8 to 7.1 ± 0.9 (P = 0.09). Arterial norepinephrine concentration decreased by −12 ± 5 %, whole-body norepinephrine spillover rate by −14 ± 8 %, and MSNA by −9 ± 5 bursts per 100 heartbeats in the HCD group (P all >0.05 versus control group). Step-wise regression analysis revealed a bidirectional relationship between enhanced exogenous insulin clearance post weight loss and reduction in calf vascular resistance (r = −0.63, P = 0.01) which explained 40 % of the variance. Increase in hepatic insulin extraction was predicted by enhanced finger reactive hyperaemic response (P = 0.006) and improvement in oral glucose tolerance (P = 0.002) which together explained 64 % of the variance. CONCLUSIONS: Insulin clearance is independently and reciprocally associated with changes in vascular function during weight loss intervention. Trial registration ClinicalTrials.gov: NCT01771042 and NCT00408850 BioMed Central 2015-08-22 /pmc/articles/PMC4546319/ /pubmed/26297500 http://dx.doi.org/10.1186/s12933-015-0276-2 Text en © Straznicky et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Original Investigation Straznicky, Nora E. Grima, Mariee T. Sari, Carolina I. Lambert, Elisabeth A. Phillips, Sarah E. Eikelis, Nina Kobayashi, Daisuke Hering, Dagmara Mariani, Justin A. Dixon, John B. Nestel, Paul J. Karapanagiotidis, Sofie Schlaich, Markus P. Lambert, Gavin W. Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss |
title | Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss |
title_full | Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss |
title_fullStr | Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss |
title_full_unstemmed | Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss |
title_short | Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss |
title_sort | reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546319/ https://www.ncbi.nlm.nih.gov/pubmed/26297500 http://dx.doi.org/10.1186/s12933-015-0276-2 |
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